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Abstract Background Aging is an irreversible progressive decline in physical function. Graves’ disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated. Methods We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R 2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I 2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes. Results F-statistics of the five IVs were greater than 10, and the R 2 values ranged from 0.033 to 0.156 (R 2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer’s disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004). Conclusions GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer’s disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging.

Abstract Background Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. Methods In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2−/−) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. Results Our results indicate that 3–4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. Conclusions Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways. Graphical Abstract

This study examines the potential impacts of projected atmospheric carbon dioxide (pCO2) levels reaching 800 ppm by the end of the century, focusing on ocean acidification effects on marine ecosystems in the coastal areas of Bohai. We investigated how acidification affects the grazing patterns of microzooplankton using dilution techniques and ecophysiological methods. Our findings indicate that acidic conditions shift the phytoplankton community structure, changing dominant species. Elevated CO2 concentrations reduced grazing pressure on phytoplankton, with less steep declines in growth rates at 800 ppm CO2 (spring: 2.43 d−1 vs. 2.16 d−1, summer: −0.46 d−1 vs. −0.73 d−1, autumn: −0.45 d−1 vs. −0.90 d−1) and significant decreases in grazing pressure percentages (%Pp from 0.84 to 0.58 and %Pi from 0.64 to 0.46). Short-term acid exposure significantly increased superoxide dismutase activity in both microplankton (from 0.03 to 0.08 U mg−1, p

Urban Park Green Space (UPGS) is an essential component of cities, with a wide range of important services. There is a keener demand for green space in the process of urbanization. Previous studies have extensively evaluated the residents’ accessibility to green space, which belonging to the demand of UPGS’s social service function, but rarely combined the ecological service demand to conduct a refined calculation. This may lead to biased results in the evaluation of the satisfaction of green space. Considering the scarcity of urban land resources, it is difficult to support the efficient use of space based on these results. To fill this gap, this study evaluated the accessibility of various service functions that UPGS can provide from a variety of demand perspectives in central Beijing using multi-source geospatial big data. The results show that: (1) The accessibility results may be overestimated when ignoring eco-service demand. (2) Regions with worse or poor accessibility have the largest proportion, and accessibility presents an obvious low–high-low cyclic structure. (3) Urban peripheral areas are always in a significant disadvantaged position in terms of accessibility. Based on the accessibility results, the solution is further provided by using PSO algorithm to simulate the location of new parks to solve the problem of insufficient UPGS supply in the low accessibility area. Our study can provide better insights for city managers to formulate effective green space management strategies and references for optimization strategy.

Abstract Transarterial chemoembolisation (TACE) is a standard therapy for hepatocellular carcinoma (HCC). However, adverse events, including abdominal pain, are common. This study aimed to investigate and verify the feasibility of a nomogram model to predict severe abdominal pain after first conventional TACE (cTACE) among patients with HCC. Patients with HCC treated with cTACE between October 28, 2019, and August 5, 2022, at a single centre were enrolled (n = 216). Patients were divided into training and validation cohorts (ratio, 7:3). A visual analogue scale score between 7 and 10 was considered severe abdominal pain. A total of 127 (58.8%) patients complained of severe abdominal pain after first cTACE treatment. The nomogram considered age and tumour number and size. The nomogram demonstrated good discrimination, with a C-index of 0.749 (95% confidence interval [CI], 0.617, 0.881). Further, the C-index in the validation cohort reached 0.728 (95% CI 0.592, 0.864). The calibration curves showed ideal agreement between the prediction and real observations, and the nomogram decision curve analysis performed well. The nomogram model can provide an accurate prediction of severe abdominal pain in patients with HCC after first cTACE, aiding in the personalization of pain management and providing novel insights into hospital nursing.

Abstract Objective This article aims at exploring the role of hypoxia-related genes and immune cells in spinal tuberculosis and tuberculosis involving other organs. Methods In this study, label-free quantitative proteomics analysis was performed on the intervertebral discs (fibrous cartilaginous tissues) obtained from five spinal tuberculosis (TB) patients. Key proteins associated with hypoxia were identified using molecular complex detection (MCODE), weighted gene co-expression network analysis(WGCNA), least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature Elimination (SVM-REF) methods, and their diagnostic and predictive values were assessed. Immune cell correlation analysis was then performed using the Single Sample Gene Set Enrichment Analysis (ssGSEA) method. In addition, a pharmaco-transcriptomic analysis was also performed to identify targets for treatment. Results The three genes, namely proteasome 20 S subunit beta 9 (PSMB9), signal transducer and activator of transcription 1 (STAT1), and transporter 1 (TAP1), were identified in the present study. The expression of these genes was found to be particularly high in patients with spinal TB and other extrapulmonary TB, as well as in TB and multidrug-resistant TB (p-value

Carbon dioxide (CO2) serves as the primary substrate for the photosynthesis of phytoplankton, forming the foundation of marine food webs and mediating the biogeochemical cycling of C and N. We studied the effects of CO2 variation on the Michaelis-Menten equations and elemental composition of Skeletonema dohrnii and Heterosigma akashiwo. CO2 functional response curves were conducted from 100 to 2000 ppm. The growth of both phytoplankton was significantly affected by CO2, but in different trends. The growth rate of S. dohrnii increased as CO2 levels rose up to 400 ppm before reaching saturation. In contrast to S. dohrnii, the growth rate of H. akashiwo increased with CO2 increasing up to 1000 ppm, and then CO2 saturated. In addition, H. akashiwo showed a slower growth rate than S. dohrnii for all CO2 concentrations, aside from 1000 ppm, and the Michaelis-Menten equations revealed that the half-saturation constant of H. akashiwo was higher than S. dohrnii. An increase in CO2 concentration was seen to significantly affected the POC: Chl-a of both S. dohrnii and H. akashiwo, however, the effects on their elemental composition were minimal. Overall, our findings indicate that H. akashiwo had a more positive reaction to elevated CO2 than S. dohrnii, and with higher nutrient utilization efficiency, while S. dohrnii exhibited higher carbon fixation efficiency, which is in line with their respective carbon concentrating mechanisms. Consequently, elevated CO2, either alone or in combination with other limiting factors, may significantly alter the relative relationships between these two harmful algal blooms (HAB) species over the next century.

In the 21st century, cardiovascular disease (CVD) has become one of the leading causes of death worldwide. The prevention and treatment of CVD remain pressing scientific issues. Several recent studies have suggested that ferroptosis may play a key role in CVD. Most studies conducted thus far on ferroptosis and CVD have supported the link. Ferroptosis mediated by different signaling and metabolic pathways can lead to ischemic heart disease, myocarditis, heart failure, ischemia-reperfusion injury, and cardiomyopathy. Still, the specific mechanism of ferroptosis in CVD, the particular organ areas affected, and the stage of disease involved need to be further studied. Therefore, understanding the mechanisms regulating ferroptosis in CVD may improve disease management. Throughout this review, we summarized the mechanism of ferroptosis and its effect on the pathogenesis of CVD. We also predicted and discussed future research directions, aiming to provide new ideas and strategies for preventing and treating CVD.

With the development of mobile positioning technology, a large number of Origin-Destination (OD) flow data with spatial and temporal details have been produced. These OD flow could give us a great opportunity to research geographical phenomena such as spatial interaction and mobility patterns. The OD flow clustering approach is an effective way to explore the main mobility patterns of the objects. At the same time, similarity measurement plays a key role in OD flow clustering. However, most of the previous OD flow similarity measurement methods failed to make full use of the spatial information of the flow including spatial proximity and geometric similarity. In this paper, we considered both position information and geometric properties of OD flow and propose a new method to measure the spatial similarity between OD flows. Specifically, the proposed method sets the neighbor threshold with the length of OD flows and the parameter $\alpha $ dynamically. Based on the constraint of the OD points’ location, the directions of the flows are implicitly restricted. The sole-parameter $\alpha $ has a practical value as it determines the maximum length difference and the maximum directional difference that can be tolerated between similar flows. The proposed method passed a simulation experiment with synthetic flows and a case study with 283,008 taxi trips in Beijing in one day. The results show that the proposed method can discover the dominant mobility pattern from a large number of flow data effectively. In the case study, the dominant flow clusters reveal the taxi mobility patterns of residents at different distances in Beijing.

Assessing park accessibility plays an essential role in providing rational recreational services for residents in a city. The perceptions and comments of residents are also important nonspatial factors for accessibility. However, there are few accessibility studies that are combined with public perceptions. Addressing this deficit, this study proposes a perception-based, multi-travel mode, two-step floating catchment area (PM2SFCA) method to calculate park accessibility. First, we quantified the selection probability of residents to parks by integrating the Huff model and the people’s perceptions towards parks. Next, under four travel modes (walking, biking, driving and public transport), we combined the Huff model and the two-step floating catchment area method to compute park accessibility. Furthermore, the Gini coefficient and the Pearson correlation coefficient were used to illustrate the proposed method compared with the traditional E2SFCA method. Based on the above, taking the area of Beijing within the Fifth Ring Road as a study area, this paper facilitated the accessibility computation. The results indicated that the spatial distribution patterns of accessibility differed greatly under the four travel modes. Even under the same travel mode, there was an uneven accessibility distribution. Areas with high accessibility were mainly concentrated in the north, and some marginal areas also presented higher accessibility to parks. The comparative analysis results suggest that our proposed method for accessibility measurements alleviates the underestimation and overestimation of accessibility values obtained by a traditional method such as the center and edge of the study area. The research explores a new research perspective for measuring park accessibility. Furthermore, this study offers better guidance for policymakers trying to optimize park spatial distribution issues.

The rapid development of the economy promotes the increasing of interactions between cities and forms complex networks. Many scholars have explored the structural characteristics of urban spatial interaction networks in China and have conducted spatio-temporal analyzes. However, scholars have mainly focused on the perspective of static networks and have not understood the dynamic spatial interaction patterns of Chinese cities. Therefore, this paper proposes a research framework to explore the urban dynamic spatial interaction patterns. Firstly, we establish a dynamic urban spatial interaction network according to monthly migration data. Then, the dynamic community detection algorithm, combined with the Louvain and Jaccard matching method, is used to obtain urban communities and their dynamic events. We construct event vectors for each urban community and use hierarchical clustering to cluster event vectors to obtain different types of spatial interaction patterns. Finally, we divide the urban dynamic interaction into three urban spatial interaction modes: fixed spatial interaction pattern, long-term spatial interaction pattern, and short-term spatial interaction pattern. According to the results, we find that the cities in well-developed areas (eastern China) and under-developed areas (northwestern China) mostly show fixed spatial interaction patterns and long-term spatial interaction patterns, while the cities in moderately developed areas (central and western China) often show short-term spatial interaction patterns. The research results and conclusions of this paper reveal the inter-monthly urban spatial interaction patterns in China, provide theoretical support for the policy making and development planning of urban agglomeration construction, and contribute to the coordinated development of national and regional cities.

During the period of rapid urbanization, the urban fringe area is the area where urban expansion occurs first, and land use change is the most active. Studying its evolution laws and characteristics is of great significance to urban planning and urban expansion, and the primary task of fringe area research is the spatial recognition and boundary division of urban fringe area. The previous methods for defining urban fringe areas are mainly divided into qualitative division based on experience and quantitative division based on indicators constructing. This research avoids the construction of index systems and the selection of mathematical models and improves the objectivity of the experiment. Based on the existing methods, this research considers the correlation between the difference of industrial distribution within cities and the urban spatial structure and spatial distribution of urban elements and considers the distance decay law of urban density. The urban fringe area in this research is defined as the distinction region of the service and manufacturing industry extending outward from the inside of the city. First, calculate the POI density of service industry and manufacturing industry. Then look for the inflection point where its density value drops sharply and get the isoline of that point. The range within the isoline is that the industry extends outward from the inner city and has reached the saturation state. Two types of industries can determine two isolines, and the belt region between those isolines is the urban fringe area. We use the urban fringe area identified from the impervious surface data to verify the result. The comparative results show that the identification method of urban fringe area based on POI works effectively, and it can successfully identify the multi-center urban core area. The method mentioned in this paper provides a new idea from the perspective of industrial activities in identifying and defining the belt region of urban fringe area.

The method for detecting and locating a Kelvin wake in the background of a two-dimensional (2-D), large-scale, random rough sea surface is studied. In this method, the large-scale, 2-D dynamic sea surface is partitioned, the correlation function between each partitioned sea surface is analyzed and extracted by the feature selective validation method, and the energy characteristic difference measures between each partitioned sea surfaces are obtained. By averaging the difference measures between the target partitioned sea surface and the adjacent sea surface, we can obtain the average value of the characteristic difference measure of each partitioned sea surface. Through the simulation and calculation, it was determined that, after the Kelvin wakes are superimposed on the partitioned sea surface, the characteristic difference measures are clearly larger than that of the partitioned sea surface without superimposed wakes. This finding shows that the method can effectively detect the changes in the sea surface wave energy caused by the wakes. The result shows that the method can accurately and efficiently identify the location of the partitioned sea surface where the Kelvin wakes are superimposed, after selecting a reasonable threshold, to realize the accurate location of the Kelvin wakes.

Ti-PLS-3, a kind of layered titanosilicates of FER topology was developed by hydrothermal synthesis with the help of using pure silica PLS-3 as seed. The Si/Ti ratio of this material can be adjusted in a wide range from 20 − ∞. The structure and active sites of Ti-PLS-3 were detected by various characterization. After mild acid treatment to eliminate the hexa-coordinated extra-framework Ti species, the resulting material turned out to be a more effective catalyst for epoxidation of 1-hexene with H _2 O _2 than reported FER type Ti-containing material Ti-FER.

In this study, the complete mitochondrial genome of T. kessleri was sequenced and characterized. The overall base composition of T. kessleri mitogenome is 29.3% for A, 32.3% for C, 15.0% for G, and 23.5% for T. The percentage of G + C content is 47.2%. The mitogenome is a circular DNA molecule of 16,754 bp in length, including a D-loop region, two rRNA genes (12SrRNA and 16SrRNA), 13 protein-coding genes (PCGs), and 22 tRNA genes. The sequence information of T. kessleri can contribute to enrich the molecular data resources about birds and could also enable the phylogenetic research and help to resolve phylogenetic relationship problems related to Turdus.

Carbon dioxide (CO2) serves as the primary substrate for the photosynthesis of phytoplankton, forming the foundation of marine food webs and mediating the biogeochemical cycling of C and N. We studied the effects of CO2 variation on the Michaelis-Menten equations and elemental composition of Skeletonema dohrnii and Heterosigma akashiwo. CO2 functional response curves were conducted from 100 to 2000 ppm. The growth of both phytoplankton was significantly affected by CO2, but in different trends. The growth rate of S. dohrnii increased as CO2 levels rose up to 400 ppm before reaching saturation. In contrast to S. dohrnii, the growth rate of H. akashiwo increased with CO2 increasing up to 1000 ppm, and then CO2 saturated. In addition, H. akashiwo showed a slower growth rate than S. dohrnii for all CO2 concentrations, aside from 1000 ppm, and the Michaelis-Menten equations revealed that the halfsaturation constant of H. akashiwo was higher than S. dohrnii. An increase in CO2 concentration was seen to significantly affected the POC: Chl-a of both S. dohrnii and H. akashiwo, however, the effects on their elemental composition were minimal. Overall, our findings indicate that H. akashiwo had a more positive reaction to elevated CO2 than S. dohrnii, and with higher nutrient utilization efficiency, while S. dohrnii exhibited higher carbon fixation efficiency, which is in line with their respective carbon concentrating mechanisms. Consequently, elevated CO2, either alone or in combination with other limiting factors, may significantly alter the relative relationships between these two harmful algal blooms (HAB) species over the next century. [ABSTRACT FROM AUTHOR]